Rudjer Boskovic Institute, Division of Molecular Medicine, Bijenicka cesta 54, 10000 Zagreb, Croatia.
The University of Zagreb School of Medicine, Salata 3, 10000 Zagreb, Croatia; University Hospital Center Zagreb, Department of Psychiatry, Kispaticeva 12, 10000 Zagreb, Croatia.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110139. doi: 10.1016/j.pnpbp.2020.110139. Epub 2020 Oct 15.
Nowadays depression is considered as a systemic illness with different biological mechanisms involved in its etiology, including inflammatory response, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and neurotransmitter and neurotrophic systems imbalance. Novel "omics" approaches, such as metabolomics and glycomics provide information about altered metabolic pathways and metabolites, as well as disturbances in glycosylation processes affected by or causing the development of depression. The clinical diagnosis of depression continues to be established based on the presence of the specific symptoms, but due to its heterogeneous underlying biological background, that differs according to the disease stage, there is an unmet need for treatment response biomarkers which would facilitate the process of appropriate treatment selection. This paper provides an overview of the role of major stress response system, the HPA axis, and its dysregulation in depression, possible involvement of neurotrophins, especially brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and insulin-like growth factor-1, in the development of depression. Article discusses how activated inflammation processes and increased cytokine levels, as well as disturbed neurotransmitter systems can contribute to different stages of depression and could specific metabolomic and glycomic species be considered as potential biomarkers of depression. The second part of the paper includes the most recent findings about available medical treatment of depression. The described biological factors impose an optimistic conclusion that they could represent easy obtainable biomarkers potentially predicting more personalized treatment and diagnostic options.
如今，抑郁症被认为是一种全身性疾病，其病因涉及不同的生物学机制，包括炎症反应、下丘脑-垂体-肾上腺（HPA）轴失调以及神经递质和神经营养系统失衡。新的“组学”方法，如代谢组学和糖组学，提供了关于代谢途径和代谢物改变的信息，以及糖基化过程的紊乱，这些紊乱受抑郁症的发展影响或导致其发展。抑郁症的临床诊断仍然基于特定症状的存在，但由于其潜在的生物学背景具有异质性，根据疾病阶段的不同而有所不同，因此需要治疗反应生物标志物来促进适当治疗选择的过程。本文概述了主要应激反应系统 HPA 轴及其在抑郁症中的失调作用，以及神经营养因子，特别是脑源性神经营养因子、胶质细胞源性神经营养因子和胰岛素样生长因子-1，在抑郁症发展中的可能参与。文章讨论了激活的炎症过程和细胞因子水平的增加，以及神经递质系统的紊乱如何导致抑郁症的不同阶段，以及特定的代谢组学和糖组学物质是否可以被认为是抑郁症的潜在生物标志物。本文的第二部分包括关于现有抑郁症治疗方法的最新发现。所描述的生物学因素得出一个乐观的结论，即它们可能代表易于获得的生物标志物，潜在地预测更个性化的治疗和诊断选择。
